As a pioneer of spacecraft technology, she patented an optical system to detect defects in a repeating pattern. At the NASA Ames Research Center, she led a research group working primarily on optical systems for automated space exploration.

As a doctoral student at Stanford, and later as a researcher at Sandia National Laboratories and NASA Ames Research Center, Ochoa investigated optical systems for performing information processing.

Ochoa is a co-inventor on three patents for an optical inspection system, an optical object recognition method, and a method for noise removal in images. As Chief of the Intelligent Systems Technology Branch at Ames, she supervised the 35 engineers scientists in the research and development of computational systems for aerospace missions. Ochoa has presented numerous papers at technical conferences and in scientific journals.

Ochoa was selected by NASA in January 1990 and became an astronaut in July 1991. Her technical assignments in the Astronaut Office includes serving as the crew representative for flight software, computer hardware and robotics, Assistant for Space Station to the Chief of the Astronaut Office, lead spacecraft communicator (CAPCOM) in Mission Control, and as acting as Deputy Chief of the Astronaut Office. A veteran of four space flights, Ochoa has logged nearly 1,000 hours in space. She was a mission specialist on STS-56 (1993), was payload commander on STS-66, and was mission specialist and flight engineer on STS-96 and STS-110 (2002).[5][6] Ochoa was in Mission Control during the Space Shuttle Columbia disaster and was one of the first personnel informed of television coverage showing Columbia's disintegration.[7] Since 2007, she served as Deputy Director of the Johnson Space Center, helping to manage and direct the Astronaut Office and Aircraft Operations, and is retired from spacecraft operations. On January 1, 2013, Ochoa made history again by becoming the first Hispanic and second female director of NASA's Johnson Space Center.[8]